This pilot study involves the technical development and clinical evaluation of a novel technique for MRI-guided high-dose-rate (HDR) prostate brachytherapy in a 1.5T horizontal bore scanner using a dedicated interventional table. We primarily hypothesize that interventional MRI-guidance enables a high-performing novel technique for tumor-targeted salvage high-dose-rate (HDR) brachytherapy associated with favorable preliminary measures of toxicity, quality of life, and local control. The technique will be prospectively evaluated in up to 46 patients with locally recurrent prostate cancer after external beam radiotherapy. The trial is designed with two therapeutic arms: a) salvage radical prostatectomy, and b) MRI-guided and tumor targeted salvage HDR brachytherapy. The study will be coordinated and closely integrated with a separate concurrent study of MRI-guided prostate biopsy (separately funded), which will be performed prior to accrual to this therapeutic study. The preliminary data acquired in this pilot study will determine the geometric limits of MRI-guided HDR brachytherapy and will be critical for the judicious conduct of a subsequent phase II clinical trial. This proposal is innovative in two fundamental ways: MRI-guidance, and specific tumor targeting for salvage HDR brachytherapy. The proposed two-year research plan seeks to address the primary hypothesis of the study through 3 specific aims. These aims will progress in parallel. In Aim 1, we will evaluate the performance of the proposed novel technique for tumor targeted MRI-guided HDR brachytherapy. In Aim 2, we will determine if tumor targeted and MRI-guided salvage HDR brachytherapy is associated with favorable preliminary measures of toxicity and quality of life. In Aim 3, we will evaluate local control outcomes with this technique, and validate the MRI delineation of tumor-targets against whole-mount radical prostatectomy specimens. Successful completion of these 3 aims will further individualize local therapy, not only for the benefit of the proportion of cancer patients for whom initial radiotherapeutic interventions have failed, but also provide valuable technical and clinical validation that these novel image-guided (IG) approaches are clinically feasible and could be applied more broadly in prostate cancer therapy. Project Narrative RELEVANCE TO PUBLIC HEALTH: Patients with recurrence of their prostate cancer after radiotherapy currently face difficult choices. Standard second-line treatments target only and all of the prostate gland and are associated with many side effects. We propose to develop and to test a minimally invasive image- guidance technique that will focus on the recurrent tumor instead of the prostate gland. In this way, we hope to improve cancer related outcomes, reduce the side effects of salvage therapy, and improve quality of life.